brivudine and Keratitis

A therapeutic trial with topical bromovinyldeoxyuridine (BVDU) plus low-dosage steroids was conducted in five patients with chronic zoster keratouveitis, who had previously received topical acyclovir (ACV) and steroids. In all cases, BVDU (plus steroids) was found to be superior to ACV (plus steroids). Yet BVDU was not able to keep the patients from having chronic relapsing varicella-zoster keratouveitis. This can probably be explained by pathophysiological reasons, i.e., the persistence and low-grade multiplication of the varicella-zoster virus in peripheral eye tissues during the chronic carrier stage. It is possible that this chronic carrier status could be obviated by vigorous antiviral treatment during the acute phase of the illness.

Topics: Administration, Topical; Adult; Bromodeoxyuridine; Chronic Disease; Clinical Trials as Topic; Dexamethasone; Drug Therapy, Combination; Female; Herpes Zoster Ophthalmicus; Humans; Keratitis; Male; Middle Aged; Ophthalmic Solutions; Pilot Projects; Recurrence; Uveitis

(E)-5-(2-Bromovinyl)-2'-deoxyuridine (1; BrVUdR) inhibits the replication of herpes simplex virus type 1 (HSV-1) and of varicella-zoster virus (VZV) in vitro at concentrations of 0.01 to 0.23 mumol/l, whereas herpes simplex virus type 2 (HSV-2) is influenced only at 5.5 to 27 mumol/l. In comparison to some classical and newly developed antiherpetics, i. e. 5-iodo-2'-desoxyuridine (2; idoxuridine, IDU), 9-beta-D-arabinofuranosyladenine (4; vidarabine Ara-A), 9-(2-hydroxyethoxymethyl) guanine (5; acyclovir, ACV) and 2'-fluoro-5-iodo-1-beta-D-aracytosine (6;FIAC) the following order of decreasing activity was found:1 greater than 6 greater than 5 greater than 2 greater than 4 (against HSV-1) and 6 greater than 2 greater than 5 greater than 1 greater than 4 (against HSV-2). The high selectivity of the antiviral effect of BrVUdR towards HSV-1 and TZV is based on the fact, that proliferation of different mammalian cell lines is inhibited by 50% only at concentrations as high as 90 to 170 mumol/l, resulting in a therapeutical index of 1000 to 10,000. Successful treatment of an HSV-1 encephalitis in mice as well as an HSV-1 keratitis of rabbits confirmed the efficiency of 1 in experimental animal infections. No toxic side effects in both local and systemic applications were observed. Promising data from cell culture and animal experiments recommend 1 as a potential candidate for the local and systemic treatment of HSV-1 and VZV infections in man.

Topics: Animals; Antiviral Agents; Bromodeoxyuridine; Cells, Cultured; Encephalitis; Herpesviridae; Herpesviridae Infections; Humans; Keratitis; Simplexvirus

As has been established in rabbits, (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) is superior to 5-iodo-2'-deoxyuridine (IDU) in the topical treatment of epithelial HSV-1 (herpes simplex virus type 1) keratitis, and superior to 5-trifluoromethyl-2'-deoxyuridine (TFT) in the topical treatment of deep stromal HSV-1 keratitis and HSV-1 uveitis. BVDU 0.1% eye drops have also proven efficacious in the treatment of patients with dendritic corneal ulcers, geographic corneal ulcers and stromal keratitis, and combined treatment of BVDU 0.1% eye drops with oral BVDU at 375 mg/day for 5 days led to a prompt healing of keratouveitis and skin lesions in patients with ophthalmic herpes zoster.

Topics: Animals; Bromodeoxyuridine; Herpes Simplex; Herpes Zoster Ophthalmicus; Humans; Keratitis; Keratitis, Dendritic; Rabbits; Uveitis

Topics: Adult; Bromodeoxyuridine; Cornea; Herpes Zoster Ophthalmicus; Herpesvirus 3, Human; Humans; Keratitis; Male

IDU (5-iodo-2'-deoxyuridine), BVDU [(E)-5-(2-bromovinyl)-2'-deoxyuridine] and placebo ointments were studied for their effects on experimental herpes simplex (type 1) keratoconjuncitivitis in rabbits. When treatment was begun 65 h after virus inoculation, both BVDU and IDU prevented development of keratitis. Both BVDU and IDU were also effective in suppressing the severity of conjunctivitis, and in this respect, BVDU proved significantly better than IDU. When treatment was started 110 h after virus inoculation, BVDU proved significantly better than IDU in promoting healing of established keratitis.

Topics: Animals; Antiviral Agents; Bromodeoxyuridine; Female; Idoxuridine; Keratitis; Keratitis, Dendritic; Male; Rabbits